DESCRIPTION (Applicant's abstract): Breathing is modulated as the result of changes in the internal and external environment (e.g. ionic concentration, pH, pCO2 and temperature) and the behavioral state of the animal. In response to these challenges, respiratory neural network activity is modified to affect the timing and intensity of respiratory events. While these changes are specific to respiration, the issue of how neural networks adapt a behavior during environmental changes is of interest to those studying many motor systems. In mammals, hyperthermia causes an initial increase in respiration frequency (RF) that serves to enhance heat loss through evaporative cooling, but heat loss mechanisms are not always effective. For example, hyperthermia associated with conditions such as fever and heat-stroke may lead to cardiac arrest, cessation of breathing (apnea) and death. In fact, hyperthermia is a major risk factor for sudden infant death syndrome. Despite these implications, little is known about the neural mechanisms underlying the temperature-induced changes in respiratory activity. In this proposal: 1) I will determine the effects of hyperthermia on respiratory activity generated in the isolated brain-stem respiratory neural network. The response of the pre- Botzinger Complex (pBC) respiratory network to hyperthermia will be characterized by integrating population pBC neural activity and quantifying changes in RF. 2) I will use patch-clamp recordings from pBC neurons to test whether changes in RF during hypothermia result from modulation of pacemaker neurons or the emergent properties of the respiratory neural network. 3) I will also use patch-clamp recordings from pBC neurons to examine if membrane properties and/or synaptic inputs in respiratory pacemaker neurons are modulated during hypothermia.